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BackgroundArachidonic acid (AA) is a polyunsaturated fatty acid, released in inflammatory disease, such as rheumatoid arthritis (RA). Cyclooxygenase (COX) and lypooxygenase (LOX) pathways have received greater attention than cytochrome P450 (CYP) pathway of AA, which also plays a significant role in RA. AA is a substrate of CYP enzymes through two different pathways: the ω-hydroxylase, and epoxygenase pathways, respectively. The epoxygenase gives rise to epoxyeicosatrienoic acids (EETs) (5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET), whereas ω- hydroxylase produces hydroxyeicosatetraenoic acids (HETEs) [1].ObjectivesThe aim of this study is to evaluate the role of Cytochrome P450 metabolites of arachidonic acid and their therapeutic targeting in rheumatoid arthritis.MethodsPubmed and Scopus databases were the main databases used to identify all the studies conformed to the eligibility criteria.ResultsCYP enzymes (CYP3A, CYP2C19, CYP2C9, CYP1A2) suppression was observed in the synovial fluid of RA patients with higher IL-6 levels. EETs inhibit bone resorption and osteoclastogenesis, have an important role in blocking inflammation by reducing TNFα, and are negatively linked with pro-inflammatory cytokines (IL-1, IL-6, IL-8)[2]. The anti-inflammatory effects of EETs are potentially attributed to peroxisome proliferator–activated receptor gamma (PPARγ) activation. EETs are also metabolized through soluble epoxide hydrolase (sEH) to dihydroxyeicsatrienoic acids (DHETs), which have a pro-inflammatory activity. On the other hand, 20-HETE deriving from CYP ω-hydroxylase pathway has pro-inflammatory effect [3]. Data have shown that the genetic variations of CYP could affect the individual susceptibility to RA [4].ConclusionsEH inhibitors (sEHi) can not only block the inflammation caused by EETs metabolite, but can also act on LOX and COX pathway, and can be used in chronic-phase arthritis to reduce both inflammation, and the pain. In a mouse model of RA, sEHi showed decent RA assessment score improvement [5]. Moreover, data suggest that sEHi inhibit also PGE2 production, and exert an additional anti-inflammatory effect in arthritis. Since NSAIDs can lead to gastric and cardiovascular problems, sEHi are considered a better pharmacological approach in inflammatory rheumatic disease. Despite the failure of some of sEHi to reach clinical trials, we believe that CYP-derived eicosanoids should be further studied as potential target in rheumatic disease. Dual inhibitors sEHI/5-LOX activating protein (FLAP) are also very promising compounds as they can inhibit leukotriene formation, without effecting the levels of anti-inflammatory pro-resolving mediators. In perspective we suggest that multiple ligands targeting different AA pathways or mediators should be further explored as potential targets for designing new compounds to treat RA patients.References[1]M. Hoxha, B. Zappacosta. CYP-derived eicosanoids: Implications for rheumatoid arthritis. Prostaglandins Other Lipid Mediat. 146 (2020) 106405.[2]X. Xu, X.A. Zhang, D.W. Wang, The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases, Adv. Drug Deliv. Rev. 63 (8) (2011) 597–609.[3]D. Panigrahy, A. Kaipainen, E.R. Greene, S. Huang, Cytochrome P450-derived eicosanoids: the neglected pathway in cancer, Cancer Metastasis Rev. 29 (4) (2010) 723–735[4]S. Puntarulo, A.I. Cederbaum, Production of reactive oxygen species by microsomes enriched in specific human cytochrome P450 enzymes, Free Radic. Biol. Med. 24 (7–8) (1998) 1324–1330[5]J. Park, M.J. Cho, H.J. Park, Analgesic effects of soluble epoxide hydrolase inhibitor in K/BxN serum transfer arthritis mouse model, Anesth. Pain Med. 14 (2019) 76–94.Disclosure of InterestsNone declared

Introduction In Italy about 45% of people aged ≥18 years are overweight/obese and might thus be more susceptible to the adverse health effects of air pollution exposure. Particulate matter ≤10 µm (PM10) represents a common pollutant of living and working environments and has been associated with increased risk of cardiovascular diseases (CVD) and hypercoagulability. Extracellular vesicles (EV) might play an important role in PM-related CVD, as they can travel in body fluids and transfer miRNAs between cells. We investigated whether PM10 exposure is associated with changes in fibrinogen levels, EV release, and EV-miRNA content in a large sample of overweight/obese adults. Methods EV concentrations were quantified by nanoparticle tracking analysis and flow cytometry. To identify altered levels of EV-miRNAs, we profiled miRNAs of 883 subjects by the QuantStudio 12K Flex Real Time PCR System. The top 40 EV-miRNAs were validated through custom miRNA plates. Statistical analyses included multiple linear regressions, mediation analysis and bioinformatics analysis. Results In a sample of 1630 overweight/obese subjects from the SPHERE (Susceptibility to Particle Health Effects, miRNAs and Exosomes) study, short-term exposure to PM10 was associated with increased release of EVs, especially those from monocyte/macrophage components (CD14+) and platelets (CD61+). Nine EV-miRNAs (let-7c-5p; miR-106a-5p; miR-143–3 p; miR-185–5 p; miR-218–5 p; miR-331–3 p; miR-642–5 p; miR-652–3 p; miR-99b-5p) were downregulated in response to PM10 exposure and exhibited putative roles in CVD. Five of these nine EV-miRNAs were mediators in the positive association between PM10 exposure and fibrinogen levels. Conclusions Our study sheds some light on the potential mechanisms underlying the adverse cardiovascular health effects of air pollution exposure. Our results were obtained in a hypersusceptible population and thus strengthen the relevance of health promotion interventions for both the general public and the working population, as they might be particularly feasible in the workplace.

BACKGROUND: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case–control studies suggested an association between short blood telomere length (TL) and increased RCC risk. METHODS: We conducted a large population-based case–control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models. RESULTS: Median TL was 0.85 for both cases and controls (P ¼0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (Po0.001 and P ¼0.07, respectively), and African Americans had longer TL than Caucasians (Po0.001). CONCLUSION: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case–control study is, to our knowledge, the largest investigation to date of TL and RCC.

In this paper, an interlaboratory comparison in the field of measurement of temperature is presented. Within the comparison, calibration of a standard platinum resistance thermometer (SPRT) by comparisons in the range from $$-80\,^{\circ }\hbox {C}$$ to $$300\,^{\circ }\hbox {C}$$ was performed. At the same time, in order to support the calibration and measurement capabilities (CMCs) entries of the participating laboratories, we have registered this as EURAMET Project 1251 (Comparison of the calibration of standard platinum resistance thermometers in the range from $$-80\,^{\circ }\hbox {C}$$ to $$300\,^{\circ }\hbox {C}$$ by comparison). It was recommended that the participants use their standard procedure for the calibration of the standard platinum resistance thermometers and follow instructions from the protocol of EURAMET Project 1251 during the temperature calibration and, if possible, avoid making extra time-consuming measurements. The interlaboratory comparison was organized by the University of Ljubljana, Faculty of Electrical Engineering, Laboratory of Metrology and Quality (MIRS/UL-FE/LMK) in the scope of the IPA 2011 project. The interlaboratory comparison included a maximum of eleven measurement points. However, certain laboratories did not perform measurements at all points in the range. They have performed only measurements in the range that they cover. Prior to the calibration by comparison in each laboratory, a test measurement at the triple point of water or ice point was done in order to assess the stability of the instruments. Results of the comparison show that all the measurements agree within declared uncertainties and thus supporting declared capabilities of the participating laboratories.

Background: Studies of immigrants represent an useful tool to determine the relative relevance of environmental vs genetic factors in causing the reported rapid increase of the prevalence of sensitization and allergic diseases. Methods: A total of 152Albanian migrants to Southern Italy responded to a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and 139 of them underwent skin prick test, and 61 serological assays for total IgE and IgG antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV-1), hepatitis A virus (HAV) and Helicobacter pylori (HP). Results: Reported asthma was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152; 15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%) subjects. The frequency of skin sensitization to pollen (P ¼ 0.003) and that of hay fever (P ¼ 0.004) increased with the time spent in Apulia. All the 61 sera had antibodies against HAV, 59/61 (96.7%) against HSV-1, 48/61 (78.7%) against HP and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever symptoms were correlated to the duration of residence in Southern Italy. Conclusions: Data presented indicate that Albanian migrants to Italy, in spite of the low prevalence of allergic diseases and sensitization in their country of origin, manifest with time an increasing prevalence of sensitization to local allergens and nasal symptoms after immigration to Italy. This would suggest a permanent role of allergen exposure and lifestyle factors in influencing the appearance of sensitization and symptoms of allergic diseases.

Background: Long-term exposure to ambient air pollution has been associated with loss of cognitive function in the elderly, but the pathways mediating this association are still unclear. Telomeres ...

Dap (Defective aleurone pigmentation) is the designation for mutations in maize that give rise to a characteristic dappled endosperm phenotype, consisting of patches of purple tissue, of variable size and shape, on a yellow background. Features shared by all Dap mutants are: dominant expression when they are maternally derived, lack of expression or transmission when they originate from pollen, failure to recover homozygous Dap genotypes, reduced frequency of Dap seeds in the progeny of outcrosses of Dap/+ females, association of the dappled phenotype with reduction in seed size. The mutants so far tested, six in all, can be grouped into two classes, one including male-transmissible (MT) isolates not expressed in the endosperm if their contribution is paternal, and a second class of isolates (NMT) that are permanently lost following paternal transmission. We suggest that the NMT mutations are on a chromosome that carries an intercalary deletion. Assuming linkage between the mutant and the deletion, selection against the deficient chromosome during male gametogenesis would account for the failure to recover Dap seeds in the progeny of Dap/+ male parents. We have obtained genetic evidence supporting this hypothesis. This interpretation, however, does not apply to MT alleles. For these, other mechanisms, such as imprinting and/or dosage effects may be proposed. The mutable pattern in the endosperm to which all Dap mutants give rise is an intriguing phenotype which remains to be clarified. An unexpected finding is that aleuronic and subaleuronic cells corresponding to the colourless areas are abnormal in shape and anthocyanin biosynthesis is blocked in these cells. This finding calls for further investigation in light of a possible connection between flavonoid precursors and cell shape.

Background and Aims: Benzene is a widespread environmental chemical that has been associated with increased risk of leukemia. Though potential carcinogenic mechanisms are still unknown, recent evid...

A sample of Kosova Basin lignite was extracted with cyclohexanol. The yield of extract was 19.98 wt%. The extract was fractionated into acidic, basic and neutral components and benzene- and petroleum ether-insoluble fractions. After ashing with HClO 4 and HNO 3 , eleven elements (K, Ca, Mg, Fe, Pb, Zn, Cu, Mn, Cr, Cd and Ni) were analysed by atomic absorption spectroscopy and seven elements (Al, Ba, Sr, Be, B, Ga and V) by inductively coupled plasma optical emission spectroscopy. A majority of the elements (Fe, B, Al, Zn, Pb, Cu, Ca, Mg, Sr, Ga and V) were found concentrated in the acidic and phenol fractions, while K, Ni, Ga and Cu predominated in the amine fraction. The metals thus analysed were associated with heteroatoms.